Calcimimetic agents and the calcium-sensing receptor

Blood ionized extracellular calcium is closely regulated. To accomplish thi s, a hormone-like receptor that is responsive to extracellular ionized calc ium regulates both the secretion of parathyroid hormone and the excretion o f urinary calcium (as well as other cellular processes). Several hereditary disorders have mutations that cause either loss or gain of function of the calcium-sensing receptor, and alterations of the calcium-sensing receptor may play a role in both primary and secondary hyperparathyroidism. Calcimim etics are agents that act to make the calcium-sensing receptor more sensiti ve to extracellular ionized calcium; thereby they suppress the secretion of parathyroid hormone. Early trials in animal models of secondary hyperparat hyroidism and in patients with primary hyperparathyroidism or with uremic s econdary hyperparathyroidism have shown that the first generation calcimime tic, R-568, effectively lowers parathyroid hormone levels and is well toler ated. Curr Opin Nephrol Hypertens 9:123-132. (C) 2000 Lippincott Williams & Wilkins.